Novel use of g-protein-conjugated receptor and ligand thereof

Abstract

The present invention provides a screening method for a substance that alters the bindability of RAIG2 or RAIG3 and glucose or 1,5-anhydroglucitol, including using RAIG2 or RAIG3 and glucose or 1,5-anhydroglucitol, and a regulator of sugar/lipid metabolism, a regulator of pancreas/pituitary function, a regulator of insulin secretion/blood glucose and ACTH secretion, and a prophylactic/therapeutic agent for a disease involved by an abnormality thereof, containing an RAIG2 or RAIG3 agonist or antagonist.

1 .- 30 . (canceled) 
     
     
         31 . A screening method for a substance that regulates sugar/lipid metabolism, comprising using RAIG2 or a partial peptide thereof or RAIG3 or a partial peptide thereof. 
     
     
         32 . The screening method of  claim 31 , wherein the substance regulates pancreas and/or pituitary function. 
     
     
         33 . The screening method of  claim 32 , wherein the substance regulates insulin secretion and/or blood glucose level, and/or adrenocorticotropic hormone secretion. 
     
     
         34 . The screening method of  claim 31 , wherein the substance is a candidate of prophylactic/therapeutic substance for a disease selected from the group consisting of diabetes mellitus, impaired glucose tolerance, ketosis, acidosis, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, hyperlipemia, eating disorder, depression, Cushing's disease, gonadal dysfunction, dermatopathies, arthropathies, osteopenia, arteriosclerosis, thrombotic disease, dyspepsia, memory and learning disorder, obesity, hypoglycemia, hypertension, edema, insulin resistance syndrome, brittle diabetes, fatty atrophy, insulin allergy, insulinoma, fat toxicity and cancers. 
     
     
         35 . The method of  claim 31 , wherein RAIG2 or a partial peptide thereof or RAIG3 or a partial peptide thereof is supplied in the form of a eukaryotic cell that produces the same. 
     
     
         36 . The method of  claim 35 , comprising further using a nucleic acid containing a base sequence that encodes RAIG2 or a portion thereof or a nucleic acid containing a base sequence that encodes RAIG3 or a portion thereof, or an antibody against RAIG2 or an antibody against RAIG3. 
     
     
         37 . The method of  claim 35 , wherein secretion of insulin or adrenocorticotropic hormone serves as an index. 
     
     
         38 . The method of  claim 35 , wherein the intracellular Ca 2+  concentration or cAMP production serves as an index. 
     
     
         39 . The method of  claim 35 , wherein the expression of a reporter or selection marker gene serves as an index. 
     
     
         40 . A screening method for a substance that alters the bindability of RAIG2 or RAIG3 and glucose or 1,5-anhydroglucitol, comprising using RAIG2 or a partial peptide thereof or RAIG3 or a partial peptide thereof, and glucose or 1,5-anhydroglucitol. 
     
     
         41 . The method of  claim 40 , wherein RAIG2 or a partial peptide thereof or RAIG3 or a partial peptide thereof is supplied in the form of a cell that produces the same. 
     
     
         42 . The method of  claim 41 , wherein secretion of insulin or adrenocorticotropic hormone serves as an index. 
     
     
         43 . The method of  claim 41 , wherein the intracellular Ca 2+  concentration or cAMP production serves as an index. 
     
     
         44 . The method of  claim 41 , wherein the expression of a reporter or selection marker gene serves as an index. 
     
     
         45 .- 56 . (canceled) 
     
     
         57 . A method of regulating sugar/lipid metabolism in a mammal, which method comprises promoting the expression or activity of RAIG2 and/or RAIG3 in an animal to regulate sugar/lipid metabolism in the animal. 
     
     
         58 . The method of  claim 57 , wherein promoting the expression or activity of RAIG2 and/or RAIG3 prevents or treats a disease selected from the group consisting of diabetes mellitus, impaired glucose tolerance, ketosis, acidosis, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, hyperlipemia, eating disorder, depression, Cushing's disease, gonadal dysfunction, dermatopathies, arthropathies, osteopenia, arteriosclerosis, thrombotic disease, dyspepsia, and memory and learning disorder. 
     
     
         59 . The method of  claim 57 , wherein promoting the expression or activity of RAIG2 and/or RAIG3 prevents or treats a disease selected from the group consisting of obesity, hyperlipemia, type 2 diabetes mellitus, hypoglycemia, hypertension, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, edema, insulin resistance syndrome, brittle diabetes, fatty atrophy, insulin allergy, insulinoma, arteriosclerosis, eating disorder, depression, Cushing's disease, thrombotic disease, fat toxicity and cancers. 
     
     
         60 . The method of  claim 57 , wherein promoting the expression or activity of RAIG2 and/or RAIG3 regulates pancreatic and/or pituitary function in the mammal. 
     
     
         61 . The method of  claim 58 , wherein promoting the expression or activity of RAIG2 and/or RAIG3 promotes insulin secretion, reduces blood glucose level, and/or regulates adrenocorticotropic hormone secretion. 
     
     
         62 . The method of  claim 57 , wherein the following (a) or (b) is administered to the mammal in an amount effective to promote the expression or activity of RAIG2 and/or RAIG3:
 (a) RAIG2 or a partial peptide thereof and/or RAIG3 or a partial peptide thereof;   (b) a nucleic acid that encodes RAIG2 or a partial peptide thereof and/or a nucleic acid that encodes RAIG3 or a partial peptide thereof.   
     
     
         63 . A method of regulating sugar/lipid metabolism in a mammal, which method comprises suppressing the expression or activity of RAIG2 and/or RAIG3 in a mammal to regulate sugar/lipid metabolism in the mammal. 
     
     
         64 . The method of  claim 63 , wherein suppressing the expression or activity of RAIG2 and/or RAIG3 regulates pancreatic and/or pituitary function in the mammal. 
     
     
         65 . The method of  claim 64 , wherein suppressing the expression or activity of RAIG2 and/or RAIG3 suppresses insulin secretion, increases blood glucose level, and/or regulates adrenocorticotropic hormone secretion. 
     
     
         66 . The method of  claim 63 , wherein the following (a) or (b) is administered to the mammal in an amount effective to suppress the expression or activity of RAIG2 and/or RAIG3:
 (a) a neutralizing antibody against RAIG2 and/or a neutralizing antibody against RAIG3;   (b) a nucleic acid containing a base sequence complementary to a base sequence that encodes RAIG2 or a portion thereof and/or a nucleic acid containing a base sequence complementary to a base sequence that encodes RAIG3 or a portion thereof.   
     
     
         67 . A method for diagnosing one or more abnormalities in a mammal, which method comprises determining the expression of RAIG2 mRNA or protein and/or RAIG3 mRNA or protein in a mammal to diagnose one or more abnormalities in sugar/lipid metabolism, pancreatic function, pituitary function, insulin secretion, blood glucose level, and adrenocorticotropic hormone secretion in the mammal. 
     
     
         68 . The method of  claim 67 , further comprising diagnosing a disease selected from the group consisting of diabetes mellitus, impaired glucose tolerance, ketosis, acidosis, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, hyperlipemia, eating disorder, depression, Cushing's disease, gonadal dysfunction, dermatopathies, arthropathies, osteopenia, arteriosclerosis, thrombotic disease, dyspepsia, memory and learning disorder, obesity, hypoglycemia, hypertension, edema, insulin resistance syndrome, brittle diabetes, fatty atrophy, insulin allergy, insulinoma, fat toxicity, and cancers.